The beta-keto ester compound of formula (1) is an important intermediate for the synthesis of various quinolone antibiotics (e.g. ciprofloxacin, levofloxacin, trovafloxacin, gemifloxacin, etc.) which show potent antibiotic activities, and so has been used as an agent for the treatment of bacterial infection of human or animal.
The beta-keto ester compound of formula (1) is generally synthesized through a three-step process (see: Synthesis, 1993, 290; Org. Prep. Proc. Int., 1997, 29, 231).
The three-step synthesis process is recently reduced to one-step process by using the Blaise reaction, in which a new zinc activation method by a catalytic amount of organic acid was established with good reproducibility (see: WO 03033469; Synthesis, 2004, 16, 2629), as shown in the following Reaction Scheme 1.

However, despite the above merits, the process using the Blaise reaction still has the following problems: (1) it is highly exothermic, and so is difficult to control the reaction heat, (2) it is difficult to handle alkyl alpha bromo acetate due to the lachrymal property, and (3) an excess amount of zinc metal having high density makes the stirring difficult, and is occasionally deposited at the bottom of the reactor, thereby lowering the reaction reproducibility.